Targeting the tumor’s micro-environment could lead to a new treatment

Metastasis refers to the migration of cancer cells from the primary tumor elsewhere in the body usually through bloodstream. It is not known why some cancers disseminate especially in the brain, so researchers at the Brain Tumor Center at the University of Cincinnati (UC) Neuroscience Institute and UC Cancer Institute, wanted to study the mechanism that underlies the occurrence of these metastases.

Statistics show that more than 170 000 people are diagnosed every year with brain metastases in the United States. Although recently there have been many advances on the treatment, the survival of patients with brain metastases still remains limited. Initially, researchers believed that blood brain barrier is to be blamed for the failure of chemotherapy, but it seems that there are other mechanisms that promote the growth of these tumors. Recently researchers have focused on certain molecules called microRNAs, which are found both in tumor cells and healthy cells. But when these molecules are disturbed, they promote the initiation and growth of the tumor.

It seems that the brain metastases are favored by the interaction between cancer cells and cells in the brain. James Driscoll, MD, PhD, assistant professor in the UC Department of Internal Medicine’s Division of Hematology Oncology and the study’s lead investigator, explained that these cancer cells are the seeds and the cells in the brain are the soil. He added that now they focus on tumor micro-environment, that is the cells (around the tumor) that feed cancer cells.

The study led by researchers at the University of Cincinnati points out that the first event is represented by the contact between the tumor cells and the astrocytes. After this contact, in tumor cells, the level of microRNA 768-3p is reduced and the level of K-Ras, a signaling molecule, increases. The increased level of K-ras promotes and sustains the development of metastases and hampers the effect of chemotherapy.

Driscoll explained that this occurs only when cancer cells and tumor cells are in direct contact and that K-ras is the main molecule that promotes tumor growth. Understanding the mechanisms involving microRNA 768-3p and K-ras could be the starting point for future therapies to stop cancer. Researchers believe that the ultimate focus is to try to block or overcome the growth promoting effect caused by tumor micro-environment. Driscoll said that they hope to move forward with these studies and to test the effectiveness of overall survival of patients with metastases.